The papillomaviruses are associated with naturally occurring carcinomas in a variety of species, including man. There are now 46 human papillomaviruses (HPVs) which have been identified in man. Twelve of these have been associated with human genital tract lesions. Of these, HPV-6 and HPV-11 have been found associated with a high percentage of benign genital warts. HPV- 16, HPV-18, HPV-31, and HPV-33 have been found in a high percentage of cervical carcinomas. We have previously identified several human cervical carcinoma lines which contain either of the integrated HPV DNA sequences. Two of the cell lines contained integrated HPV-16 DNA, and in each of these cell lines the genomes were transcriptionally active. Genomic clones have been made from each of these HPV-16 positive lines and have been characterized. In the SiHa cell line in which only a single copy of the HPV-16 genome is integrated, the cellular flanking sequence have been sequenced. Integrated has occurred in the E2 ORF of the HPV-16 genome. We have characterized a conditional enhancer in the control region of the HPV-16 genome and have shown that the E2 gene of HPV-16 encodes a transcriptional transactivating function that induces this enhancer element. Further genetic analysis has mapped an additional transacting function to be the HPV-16 E7 gene. This factor can transactivate the adenovirus E1a gene product. It can also complement ras in the transformation of primary rat embryo cells.